Purpose of Review

According to the amyloid cascade hypothesis, removing amyloid beta (Aβ) should cure Alzheimer’s disease (AD). In the past three decades, many agents have been tested to try to lower Aβ production, prevent Aβ aggregation, and dissolve Aβ deposits. However, the paucity in definitive preventative or curative properties of these agents in clinical trials has resulted in more avant-garde approaches to therapeutic investigations. Immunotherapy has become an area of focus for research on disease-modifying therapies for neurodegenerative diseases. In this review, we highlight the current clinical development landscape of monoclonal antibody (mAb) therapies that target Aβ plaque formation and removal in AD.

Recent Findings

Multiple potential disease-modifying therapeutics for AD are in active development. Targeting Aβ with mAbs has the potential to treat various stages of AD: prodromal, prodromal to mild, mild, and mild to moderate. Monoclonal antibodies discussed here include aducanumab, lecanemab, solanezumab, crenezumab, donanemab, and gantenerumab.

Summary

The final decision by the FDA regarding the approval of aducanumab will offer valuable insight into the trajectory of drug development for mAbs in AD and other neurodegenerative diseases. Future directions for improving the treatment of AD will include more inquiry into the efficacy of mAbs as disease-modifying agents that specifically target Aβ peptides and/or multimers. In addition, a more robust trial design for AD immunotherapy agents should improve outcomes such that objective measures of clinical efficacy will eventually lead to higher chances of drug approval.

中文翻译：

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AD 中淀粉样蛋白降低剂的严格评价

 审查目的

根据淀粉样蛋白级联假说，去除β淀粉样蛋白（Aβ）应该可以治愈阿尔茨海默病（AD）。在过去的三十年中，已经测试了许多药剂来尝试降低 Aβ 产生、防止 Aβ 聚集和溶解 Aβ 沉积物。然而，临床试验中这些药物缺乏明确的预防或治疗特性，导致治疗研究需要更前卫的方法。免疫疗法已成为神经退行性疾病疾病缓解疗法研究的重点领域。在这篇综述中，我们重点介绍了针对 AD 中 Aβ 斑块形成​​和去除的单克隆抗体 (mAb) 疗法当前的临床开发前景。

 最近的发现

多种潜在的 AD 疾病缓解疗法正在积极开发中。使用 mAb 靶向 Aβ 有可能治疗 AD 的各个阶段：前驱期、前驱期至轻度、轻度和轻度至中度。这里讨论的单克隆抗体包括 aducanumab、lecanemab、solanezumab、crenezumab、donanemab 和 gantenerumab。

 概括

FDA 关于批准 aducanumab 的最终决定将为 AD 和其他神经退行性疾病的 mAb 药物开发轨迹提供有价值的见解。改善 AD 治疗的未来方向将包括更多地研究单克隆抗体作为专门针对 Aβ 肽和/或多聚体的疾病缓解剂的功效。此外，针对 AD 免疫治疗药物的更稳健的试验设计应该可以改善结果，从而客观地衡量临床疗效，最终将提高药物批准的机会。